1794-P: The Effects of Amyloid Formation in Human Islets on Islet-Derived Extracellular Vesicles
Bibliographic record
Abstract
Introduction and Objective: Progressive loss of beta-cell mass and function associated with islet inflammation is a key defect in type 2 diabetes (T2D). Islet amyloid, formed by aggregation of the beta-cell hormone, human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and beta-cell failure in T2D, but the cellular mechanisms are still unclear. Here, we examined the effects of amyloid formation in human islets on the characteristics of islet-derived extracellular vesicles (EVs), as a potential mediator of amyloid-associated islet inflammation. Methods: Isolated human islets (purity 90-95%; dithizone) from cadaveric pancreatic donors (n=3) were cultured at normal (5.5 mmol/L) or elevated (11.1 mmol/L) glucose for 7 days. Small EVs (sEVs) were isolated from the culture medium collected on day 3 or 7, characterized by tunable resistive pulse sensing (TRPS) technique, and purity assessed by sEV markers. (Pro)hIAPP forms were detected in purified sEVs by Western blot. Islet IL-1 beta production, amyloid formation, beta-cell Fas upregulation, and apoptosis were assessed by quantitative immunolabelling. Results: Human islets progressively formed amyloid during 7-day culture at elevated (but not normal) glucose, associated with elevated islet IL-1beta production, beta-cell Fas upregulation and apoptosis. These changes correlated with increased number and size of sEVs released from amyloid-forming islets following 3- and 7-day culture. Also, sEVs released from amyloid-forming islets contained higher levels of (pro)hIAPP forms than sEVs released from islets cultured at normal glucose which did not form amyloid. Conclusion: In summary, these data show an increase in the number, size, and (pro)hIAPP content of sEVs released from amyloid-forming human islets associated with elevated islet IL-1 beta production and beta-cell apoptosis, suggesting that islet-derived sEVs may play a role in amyloid-mediated islet inflammation in T2D. Disclosure R. Tyagi: None. B. Ozerklig: None. A. Saleem: None. L. Marzban: None.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".